Characterisation of oestrogenic properties of Isoflavones derived from Millettia griffoniana Baill. [Elektronische Ressource] : molecular mode of action and tissue selectivity / vorgelegt von Germain Jean Magloire Ketcha Wanda
151
pages
Deutsch
Documents
2006
Le téléchargement nécessite un accès à la bibliothèque YouScribe Tout savoir sur nos offres
151
pages
Deutsch
Ebook
2006
Le téléchargement nécessite un accès à la bibliothèque YouScribe Tout savoir sur nos offres
Publié par
Publié le
01 janvier 2006
Nombre de lectures
34
Langue
Deutsch
Poids de l'ouvrage
1 Mo
Publié par
Publié le
01 janvier 2006
Nombre de lectures
34
Langue
Deutsch
Poids de l'ouvrage
1 Mo
Characterisation of oestrogenic properties of
Isoflavones derived from Millettia griffoniana Baill.:
-Molecular mode of action and tissue selectivity
Dissertation
zur Erlangung des akademischen Grades
Doktor rerum naturalium (Dr. rer. nat.)
Der Fakultät Mathematik und Naturwissenschaften
der Technischen Universität Dresden
vorgelegt von
M.Sc. Germain Jean Magloire Ketcha Wanda
aus Bantoum I, Kamerun
eingereicht am 12.05.2006
Gutachter: Prof. Dr. habil. Günter Vollmer
Prof. Dr. habil. Herwig O. Gutzeit
Priv. Dz. Dr. habil. Patrick Diel
Datum der Verteidigung: 20.07.2006
Gedruckt mit der Unterstützung des Deutschen Akademischen Austauschdienstes
(DAAD)
Dedication
I dedicate this work to:
- My wife Bergeline Tchangoue Epouse Ketcha
- Borell Njonkoe Ketcha
- Loic Vianney Towa Ketcha Astrid Owona
Table of contents
Table of contents
Table of contents.................................................................................................................i
List of tables .......................................................................................................................v
List of figures .....................................................................................................................v
List of abbreviations...................................................................................................... viii
Summary ............................................................................................................................x
1 Introduction...1
1.1 current state of knowledge .................................................................................................... 1
1.2 Aim of the study.................................................................................................................... 2
1.3 Approach to the study..... 3
1.4 Thesis outline ........................................................................................................................ 3
2 Background and literature review ................................................................................5
2.1 Oestrogens............................................................................................................................. 5
2.1.1 Synthesis of oestogens..................................................................................................................5
2.1.2 Endogenous sources of oestrogens ...............................................................................................6
2.1.3 Transport and metabolism of oestrogens......................................................................................7
2.2 Physiological actions of oestrogens ...................................................................................... 7
2.2.1 Actions on the female reproductive system..7
2.2.2 Oestrogenic effects on the cardiovascular system ........................................................................8
2.2.3 Effects on bone.............................................................................................................................8
2.3 Oestrogen receptors............................................................................................................... 9
2.3.1 Discovery of oestrogen receptors........9
2.3.2 Structural and functional domains of oestrogen receptors..........................................................10
2.3.3 Distribution of oestrogen receptors ............................................................................................11
2.3.4 Regulation of oestrogen receptors ..............................................................................................12
2.4 Mechanism of Action of oestrogens.................................................................................... 13
2.4.1 Classical gene regulatory pathway (for oestrogen action)13
2.4.1.1 Oestrogen Response Element .............................................................................................13
2.4.1.2 Coactivators and corepressors of oestrogen receptors ........................................................14
2.4.2 ERE-independent pathways........................................................................................................15
2.4.2.1 AP-1 pathway .....................................................................................................................15
2.4.2.2 SP1 pathway .......................................................................................................................16
2.4.2.3 NF- κB pathway...................................................................................................................16
2.4.3 Non genomic pathway................................................................................................................17
2.4.3.1 Phosphatidylinositol 3-kinase (PI3K)-Akt Pathway ...........................................................17
2.4.3.2 Mitogen activated protein kinase (MAPK) pathway18
2.4.4 Oestrogen-independent pathways...............................................................................................18
2.5 Oestrogen antagonists or antiestrogens............................................................................... 19
2.5.1 Selective oestrogen receptor modulator (SERM) .......................................................................19
2.5.2 Pure oestrogen antagonists/ antioestrogens.20
2.6 Oestrogen disruptors/environmental oestrogens ................................................................. 21
2.6.1 “Xeno-oestrogens” .....................................................................................................................21
2.6.2 Synthetic oestrogens...................................................................................................................21
2.6.3 Phytoestrogens............................................................................................................................21
2.6.3.1 Isoflavones..........................................................................................................................22
i Table of contents
2.6.3.2 Flavonoids...........................................................................................................................23
2.6.3.3 Lignans ...............................................................................................................................23
2.6.3.4 Coumestans............23
2.7 Millettia griffoniana ............................................................................................................ 24
2.7.1 Botanical studies/distribution .....................................................................................................24
2.7.2 Description of plants of the genus Millettia................................................................................24
2.7.3 Phytochemistry/active constituents ............................................................................................24
2.7.4 Traditional use and application of Millettia griffoniana .............................................................25
2.8 Oestrogen-responsive genes used as marker genes 25
2.8.1 Cytochrom C oxidase (1A).........................................................................................................25
2.8.2 Proliferating cell nuclear antigen (PCNA)..................................................................................26
2.8.3 Ki-67...........................................................................................................................................26
2.8.4 Cyclin D1 (CD1) ........................................................................................................................26
2.8.5 Complement component 3 (C3)..................................................................................................26
2.8.6 Calcium binding protein 9 kilo Dalton (CaBP 9kD) ..................................................................27
2.8.7 Progesterone receptor (PR).........................................................................................................27
2.8.8 Vascular endothelial growth factor (VEGF) and VEGF-receptor 2 (VEGFR-2) .......................27
2.8.9 Clusterin (CLU)................28
2.8.10 Cyclooxygenase 2 (COX 2)......................................................................................................28
2.8.11 Insulin like growth factor 1 (IGF-1) .........................................................................................29
2.8.12 Insulin like growth factor binding protein 1 (IGFBP-1)...........................................................29
2.8.13 Carbonic anhydrase 2 (CA 2) ..........................................................................................
